Biosecurity and The Evolving Concern regarding dual-use · smuggle 22 vials genetic m aterial out of the country. Some vials contained Ebola virus genes, subsequently deemed non-infectious

WHAT HAS CHANGED, AND WHAT MUST BE ADDRESSED

2017 BIOSECURITY AND THE EVOLVING CONCERN REGARDING DUAL-USE

Office of Risk Management

August 2017

University of Ottawa https://orm.uottawa.ca/programs/biosafety Office of Risk Management [email protected]

Created on: June 20, 2017 Current as of: Aug. 28, 2017 1

INTRODUCTION

Biosecurity is a word that has been introduced into the regulatory framework with alarming regularly. Yet within the university community research direction is rarely directed to synthesis or modifying biological agents to make them more pathogenic, virulent, or to be candidates for malicious or dual use. For this reason the prospect of biosecurity concern is difficult to comprehend.

To understand the basis of the development of biosecurity oversight requirements, one must appreciate the issues driving the process in terms of the global perspective, technological advancements and accessibility to both information and materials which may pose new threats associated with the use of biological agents.

Strategic Initiatives, international partnerships, innovation and emerging technologies raise both the prospective of great beneficial discoveries, while at the same time represent a potential risk. This document will highlight some of the key issues.

HISTORICAL INCIDENTS and TRENDS

Founding events that lead to the development of biosecurity concerns can be traced back to the emergence of HIV, use of anthrax as an agent for terrorism, reconstruction of the influenza strain responsible for the Spanish flu, theft of Yesinia pestis from a laboratory amoung others referenced.

Appendix A - Recent and Historical Significant Events Pertaining To Biosecurity.

Current events such as those listed below ensure biosecurity fears remain in the forefront of legislative change.

2017 Lab scientists in Canada at the University of Alberta have synthesized horsepox, an extinct relative of the smallpox virus, using segments of mail-order DNA. The University of Alberta scientists acknowledged to the Washington Post that their work, should it be published, could be interpreted as sharing "instructions for manufacturing a pathogen."

2014 Discovery of 6 smallpox samples in an abandoned group of 300 lab samples that were in an unsecured Food and Drug Administration (FDA) cold-storage room during preparations for a move to the FDA's main campus

2013 New botulinum neurotoxin (BuNT/H) identified with no antitoxin available. Researcher sought guidance from the US Government. Discovery published but without the sequence data.

2012 Two former Canadian Food Inspection Agency researcher intercepted with 17 vials of pathogens, some containing Brucella bacteria, preparing to leave Canada

https://orm.uottawa.ca/programs/biosafety



2009 A former researcher at the National Microbiology Lab in Winnipeg charged with trying to smuggle 22 vials genetic material out of the country. Some vials contained Ebola virus genes, subsequently deemed non-infectious and associated with vaccine development.

THREAT Historically the threat assessment focused on international state conflict and limited to military security. It now encompasses:

• health, environmental degradation, climate change, organized crime, refuge migration, and terrorism,

• threat arising from transnational, international, and non-state actors, and • focus on individual, group and community security versus solely state security.

The biosecurity debate revolves around:

• Are naturally occurring infectious disease a security threat? • Do laboratory activities and advances in biotechnology pose a threat? • What is the proper balance in biological life science between openness and security? • What is an acceptable cost in terms of prevention of a biological threat and reacting to that

threat?

The threat is also now being evaluated in terms of the social, economic and environmental impact on Canada being:

• able to fulfill its international obligations, • avoid loss of revenue (health care, agriculture, aquaculture, forestry...), and • prevent transfer of material, knowledge and individual.

BIOSECURITY Biosecurity is defined as the measures designed to prevent the loss, theft, misuse, diversion or intentional release of pathogens, toxins and other related assets (e.g., personnel, equipment, non-infectious material, and animals) and restricted knowledge. Over time this definition reflects the expansion of the term away from solely the pathogenic agent risk to all activities related to the research.

Risk Assessment Security

Policy / Regulatory Response




Biosecurity applies to:

• agriculture (crops and livestock), • human and zoonotic agents and the environmental concerns, • prevention or limiting the transmission of infectious pathogens or pest to animals or crops, • to include risks to the economy associated with invasive non-indigenous species, • also included genetically modified organism (GMO), and • potentially restrict knowledge transfer.

In response to the biological terrorist threat the definition was expanded in the late 1990’s to include the protection of microbial agents from loss, theft, diversion or intentional misuse. Dual Use threat was added to the definition of biosecurity in 2004 by the US National Science Advisory Board in response to the 2001 Bioterrorism Anthrax Incident. The concept was extended beyond just the pathogenic agent to consider:

• techniques and technologies that can be used to create new pathogenic organisms or biologically active compounds,

• synthetic biology, • systems biology, • gene therapy, • RNA interference, and • genomics, neurobiology and immunology capacity to contribute to the development of

biological weapons. National Academies of Science has since expanded to be security against the inadvertent, inappropriate or intentional malicious or malevolent use of potentially dangerous biological agents or biotechnology including the: development, production, stockpiling or use of biological weapons as well as outbreaks of newly emergent and epidemic disease. PHAC has also their review to cover a similar scope of activities.

origins in prevention of naturally occuring pest and infectious disease

(crops, livestock)

human and zoonotic agents invasive species included biological terrorist threat

identifieddual use concept

incroporated

Regardless of the source of the definition, it is the ever expanding definition that is important to note.




DUAL USE RESEARCH OF CONCERN (DURC) While PHAC defines dual use as “Qualities of a pathogen or toxin that allow it to be either used for legitimate scientific applications (e.g., commercial, medical, or research purposes), or intentionally misused as a biological weapon to cause disease (e.g., bioterrorism)”, which also includes: data, methodology, intermediate and final products.

The National Institute of Health in the United States has expanded the definition to: “Life science research that, based on current understanding, can be reasonably anticipated to provide knowledge, information, products or technologies that could be directly misapplied to pose a significant threat with broad potential consequence to public health and safety, agricultural crops and other plants, animals, material or national security.” This is of importance for US funded research or collaborations.

In assessing this risk, there are inherent bias embedded into life science research which must be recognized, these include principles such as:

• Research by its nature is to push beyond the known, • The principle of “primum non-nocere” (above all, do no harm) is a founding principle, and • the Canadian judicious system is based on the presumption of innocence.

Fundamentally the dual-use concern is based on:

• accessibility of information and materials, • advancement of technology, and • gain-of-function (GOF)

It is recognized that the benefit gained in undertaking DURC can justify proceeding in some cases. Hence there is a reliance on the process of the evaluation of the associated risk and the ability to eliminate the risk or to mitigate it if elimination is not achievable. The Seven Deadly Sins: “The Biotechnology Research in an Age of Terrorism Report” identified what it considered to be ‘experiments of concern’, or what are colloquially known as ‘the Seven Deadly Sins’:

1. demonstrating how to render a vaccine ineffective, 2. conferring resistance to therapeutically useful antibiotics or antiviral agents, 3. enhancing the virulence of a pathogen or rendering a non-pathogen virulent, 4. increasing transmissibility of a pathogen, 5. altering the host range of a pathogen, 6. enabling the evasion of diagnostic/detection modalities, or 7. enabling the weaponization of a biological agent or toxin.




Resources and Procedures for determining dual use risk are found in: Appendix B Decision Tree: Identification of Dual-Use Potential in Life Science Research Appendix C uO Biosecurity and Dual Use Research of Concern: Identification, Evaluation, and

Mitigation Guide. Literature Review: Although the following findings indicate the evidence of “dual-use research of concern” risk remains low; there is still a legal obligation in Canada and under the University’s Human Pathogen and Toxins Licence to identify, evaluate, and mitigate any potential dual-use risk research. 2003 American Society of Microbiology reviewed 16,000 manuscripts of which 3 were deemed to

require additional dual-use review. (Potential risk of 0.02%) 2005-2008 Nature Publishing Group reviewed 74,000 manuscripts of which 28 were deemed of

potential dual-use concern. (Upon review none were subsequently rejected). (Potential risk of 0.04%)

Up to 2014 Danish Centre for Biosecurity and Biopreparedness that licences new technology (some

with the potential for weaponization) did not identify any meeting dual use research concerns.

To 2017 NIH in reviewing funded research has not revoked funding due to a dual-use potential.

RISK ASSESSMENT The risk assessment process is designed not necessarily to stop DURC, but to allow the risk and benefit to be assessed and to determine what mitigation and communication strategies need to be deployed to ensure the safe use and dissemination of information to be achieved.

Remember that risk is often expressed as an equation (Risk=Impact X Probability / Cost), so while there is a potential one must evaluate what the probability is, or the potential cost implications.

To delineate risk for DURC, and thereby minimize comprehensive review of all projects, a risk scale is been applied.

While reporting remains low, this must be considered in terms of the on-going concerns being reported (see Appendix A).




Category 1 Low risk exist as the material is either risk group 1 or 2 and the research has not been identified as having a potential DURC classification.

Category 2 Risk Group 2 material that has been modified such that there is a potential DURC risk.

Category 3 Security Sensitive Biological Agent or Toxin is being used, and/or associated technology, knowledge or product is deemed to meet the definition of DURC.

Note: the following acronyms will be used to denote the categories: DURC-1, DURC-2 DURC-3.

TRAINING AND EDUCATION While it may be easy to disregard the risk; failure to do so will only justify regulators to increase the requirements for additional controls to be put in place which may not be required if diligence is applied throughout the life span of the research. A security culture will ensure your research property (material and intellectual) will be protected.

Developing the appropriate biosecurity culture requires continuous education, communication and enforcement. This document supports this goal.

Dual use activities require specific and more rigours training then the basic Principles of Biosafety, and will be tailored to the research at hand, with the involvement of the Office of Risk Management under the authority of the Biosafety Program.

IMPLICATIONS FOR RESEARCH Biosecurity framework within the research laboratory is comprised of 7 key activities:

1. Physical requirements, 2. Personnel management, 3. Material control, 4. Accountability, 5. Information security, 6. Transportation security, and 7. Program management.

All parties in the laboratory are responsible for full filling these requirements, regardless if they are involved in the DURC project or not. Risk Assessments must be reviewed annually or whenever experimental factors change, which would nullify the existing risk assessment: changes in experimental procedures, new experimental results, new sources of funding or collaborations, changes in personnel or inventory…




The University also adopts the following biosecurity framework, as good management practices for dual-use research management:

• guidelines, • awareness, • ongoing mandatory education, • evaluation and review of research for dual-use potential, • risk assessment and risk management, • periodic evaluation and • compliance

CLOSING REMARK

IT ONLY TAKES ONE PERSON TO CHANGE THE FACE OF REGULATIONS, RESEACH AND PUBLIC SECURIITY.

October 2001 U.S. Anthrax letter Source: http://www.selectagents.gov




REFERENCES International Security, Volume 34, Number 4, Spring 2010, pp. 96-132 (Biosecurity Reconsidered – Calibrating Biological Threat and Responses, G. Koblenz )

Science and Security in a Post 9/11 World: A Report Based on Regional Discussions Between the Science and Security Communities Committee on a New Government-University Partnership for Science and Security, National Research Council

SANDIA REPORT (SAND2010-6487)Printed October 2010, Biosafety Risk Assessment Methodology Susan Caskey*, Jennifer Gaudioso,Shigematsu++, George Risi+++Esmeralda Prat** Prepared by Sandia National Laboratories Albuquerque, New Mexico 87185 and Livermore, California 94550


APPENDIX A RECENT HISTORICAL SIGNIFICANT EVENTS PERTAINING TO BIOSECURITY

The following legend is designed to categorize the risk or potential risk associated with the incident: U - unauthorized access, use, possession or theft I - inventory or other documentation inadequate E – exposure, emerging or new pathogens R - release T - training, knowledge inadequate.

Note This table does not address plant and aquatic biosecurity concerns,nor the impact on trade, the economy or international agreements. Nor does this list include incidents beyond the US and only a very limited number from Canada. U I E R T

2017 July 11 (UPI) -- Lab scientists in Canada at the University of Alberta have synthesized horsepox, an extinct relative of the smallpox virus, using segments of mail-order DNA. The University of Alberta scientists acknowledged to the Washington Post that their work, should it be published, could be interpreted as sharing "instructions for manufacturing a pathogen."

e

2015 US Military inadvertently ships live anthrax to 51 labs in US (17 states) Canada,Australia and S.Korea. Samples not properly irradiated and mislabelled, 22 people treated for possible exposure i e r

2014 Discovery of 6 smallpox samples in an abandoned group of 300 lab samples that were in an unsecured Food and Drug Administration (FDA) cold-storage room during preparations for a move to the FDA's main campus. i e r

2013 New botulinum neurotoxin(BuNT/H) identified with no antitoxin available. Researcher sought guidance from the US Government. Discovery published but without the sequence data. u e

2012 2 former Canadian Food Inspection Agency researcher intercepted with 17 vials of pathogens, some containing Brucella bacteria, preparing to leave Canada u i e

2011 Researcher discovered modified variant of H5N1 avian influenza was transmissible by aerosols to ferrets. e 2009 Ipsen Ltd pharmaceutical company based in France accused of aiding Irans biological weapon capacity by selling

medicinal product based on botulinium toxin to the University of Teran and Pasteur Institute in Iran. e r

2009 H3N2 human influenza sample, contaminated with H5N1 avian influenza sent from Baxter International Plant in Austria to a research company who discovered the contamination. Risk human and avian influenza could produce a hybrid which could result in a pandemic.

i e r

2009 Colorado suricgial technician accused of potentially infecting patients with hepatitis C, as a result of sustaining drug habit by stealing fentanyl and replaced used ones with ones refilled with saline and tainted with thier own blood. u i e

2009 Postdoctoral fellow at US university, meticulously and systematically sabotaged work over a 3 month period 2009 Fired cardiologist broke into lab 3 times, charged with theft>$10,00 and transporting stolen materials to Russia 2009 A former researcher at the National Microbiology Lab in Winnipeg charged with trying to smuggle 22 vials genetic

material some contained Ebola virus gene which were non infectious . u i



2009 US Army Medical Research Institute of Infections disease discovered more than 9, 200 unrecorded disease samples (working stock accumulated by researches who had left the institution prior to the new inventory system being implemented).

u i e

2008 University of Medicine and Dentistry in Newark New Jersy could not account for 2 dead mice infected with Yersinia pestis i

2007 Foot and Mouth Disease released into the environment from a lab in the UK resulting in a local outbreak. Improper waste treatment. e r

2007 Texas A&M 3 vials of Brucella abortus missing, at least 7 incidents of unauthorized access, unauthorized research, failure to fill in proper personnel registrations for select agents and toxins, failure to have a security plan, lack of access records, personnel records did not agree with authorized personnel, repeated biosafety containment failures, lack of operational and procedural safety guards during SA experiments, failure to apply medical entry requirements, lack of medical surveillance program, failure to report restricted aerosolization experiments with Coxiella brunetii on 9 occasions, lack of primary containment barriers, carcass not disposed of appropriate, lack of ppe (labcoats not worn as required). Lack of training and training records, lack of emergency response plan

u i e r t

2006 US National Security Strategy includes pandemic disease as a threat to national security in the same category as terrorist acquisition to nuclear , biological and chemical weapons

2006 19 vials of HIV Positive Blood stolen from hospital U I e 2005 University of California-Berkeley, report receiving dozen of samples thought to be harmless but contained Rocky

Mountain Spotted Fever i e

2005 CDC researchers and their colleagues successfully reconstructed the influenza A (H1N1)virus that caused the 1918-19 flu pandemic e r

2005 UN Secretary General pledges to use his to call Security Council to address overwhelming outbreak of disease 2005 University of Medicine and Dentistry in Newark New Jersy, found 3 live mice infected with Yersinia pestis missing from

separate cages. u i e t

2004 UN High Level Panel on Threats calls for greater effort against biological security challenges (infectious disease and biological terrorism), National Science Advisory Board on Biosecurity (to advise, guide and lead regarding dual-use research, Select Agent List created

2004 Improper heat-inactivated anthrax samples sent to Oakland Children’s Hospital , 7 lab personnel possibly exposed, possible emergence of heat-resistant strain of anthrax e r

2003-2005

8 state, local, private and commercial labs using SA inspected: 4 had incomplete inventory or access records, 5 had insufficient security plans (3 of which were not prevent theft, missing policies and procedures, 4 lacked training, 3 emergency response plans did not meet the standard, 3 had weak access control

u i e r t




2003-2004

15 Universities reviewed for SA, 8 had deficient inventory and/or access records,6 had weakness in security plan (4 had not used systematic approach, 3 had not provided to training or not training records, 3 emergency response plan did not address one or more areas,6 had access control weakness including ecard access.

t

2003 Professor Thomas Butler was arrested for removing 30 vials of Yesinia pestis from a laboratory. u i e r 2003 Re-emergence of H5N1 (avian flu) r r 2003 Speculation of biological weapon threat being developed by Iraq u i e r 2002-2003

11 Universities reviewed for SA security, had inadequate inventory and record keeping procedures, physical security weaknesses, at least had inadequate procedures to identify barred persons, 5 used information technology all exhibited had embedded security weakness .

u i

2002-2003

134 alleged violations of exporting toxins (listed on the Australia List) without appropriate licence to Canada by EMD Bioscience, USA . the Company also had a 171 similar charges (1992-94) u

2002 Artificially chemical synthesis of polio virus 2002 Severe acute respiratory syndrome (SARS) emerges for the first time 2001 - Anthrax terrorist attack – (Perpetrated by Scientist at US Army Medical Research Institute of Infections Disease

(USAMRID)) - Australian Groups 5th Review of Biological Weapons Convention (Canada is a member)

u i e r

2000 In Russia, eight children (ages 11-14)became ill after playing with discarded small pox vaccines e r 2000 US National Security Council names a disease as a threat HIV/AIDS 2000 UN Security Council Identifies a health issue as a threat to security (first time in 45 years)(HIV)


APPENDIX B DECISION TREE: IDENTIFICATION OF DUAL-USE POTENTIAL IN LIFE



APPENDIX C UO BIOSECURITY AND DUAL USE RESEARCH OF CONCERN: IDENTIFICATION, EVALUATION, AND MITIGATION GUIDE.

PURPOSE:

As required by the Canadian Government, it is important to determine if research activities may meet the classification of Dual User Research of Concern (DUCR). If the potential has been identified a risk assessment to identify to determine if the potential benefits of the research out weight the risk, and if so can the risk be mitigated. This Guide will assist in undertaking this process.

TARGET AUDIENCE:

• Principal Investigators • Dual Use Research of Concern Biosafety Sub-Committee

DEFINITION OF DURC While PHAC defines dual use as “Qualities of a pathogen or toxin that allow it to be either used for legitimate scientific applications (e.g., commercial, medical, or research purposes), or intentionally misused as a biological weapon to cause disease (e.g., bioterrorism)”, which also includes: data, methodology, intermediate and final products.

The National Institute of Health in the United States has expanded the definition to: “Life science research that, based on current understanding, can be reasonably anticipated to provide knowledge, information, products or technologies that could be directly misapplied to pose a significant thereat with broad potential consequence to public health and safety, agricultural crops and other plants, animals, material or national security.” This is of importance for US funded research or collaborations.

QUALIFICATION CRITIERIA FOR A DURC REVIEW To delineate risk for DURC, and thereby minimize comprehensive review of all projects, a risk scale has been applied. To qualify the research must meet either a category DURC Category 2 or 3, as described below.

Identification, Evaluation And

Mitigation Guide

BIOSECURITY AND DUAL-USE RESEARCH OF

CONCERN




Category 1 Low risk exist as the material is either risk group 1 or 2 and the research has not been identified as having a potential DURC classification.

Category 2 Risk Group 2 material that has been modified such that there is a potential DURC risk. Risk Group 2 material that has been modified such that the following potential risk exists:

8. demonstrating how to render a vaccine ineffective, 9. conferring resistance to therapeutically useful antibiotics or antiviral agents, 10. enhancing the virulence of a pathogen or rendering a non-pathogen virulent, 11. increasing transmissibility of a pathogen, 12. altering the host range of a pathogen, 13. enabling the evasion of diagnostic/detection modalities or 14. enabling the weaponization of a biological agent or toxin.

These are considered “experiments of concern”, or what are colloquially known as ‘the Seven Deadly Sins’

Category 3 Security Sensitive Biological Agent or Toxin (Appendix C) is being used, and/or associated technology, knowledge or product is deemed to meet the definition of DURC.

While the use of a SSBA will require additional security clearance by the Public Health Agency of Canada (PHAC), a comprehensive review may not be required if the “experiments of concern” are not planned. Note that annual reviews must be taken to ensure the research has not inadvertently incorporated the “experiments of concern”.

Note: the following acronyms will be used to denote the categories: DURC-1, DURC-2 DURC-3 .

REVIEW PROCESS

1. Verify if the research actually meets DURC criteria. Note: To be confirmed with PHAC is the ability to excluded are attenuated* SSBA genes of SSBA, in-silico experiments such as bioinformatics approaches , modeling experiments, health impact modeling of toxins, vaccine delivery methods, surveillance mechanisms), as this would align with US funding requirements.

* Verify the proof of non-attenuation of material.

2. Review the Principal Investigators (PI) assessment of DURC potential and supporting rationale. Review the PI assessment of the aims of the research products and can reasonably anticipated to produce one or more the applicable “experiments of concern”.

3. Conduct a risk assessment to determine what DURC criteria are involved, and the implications. Points to consider include: the




a) The ways in which knowledge, information, technologies or products form research could

be used to harm: people, crops, animals, environment, economy or security. - What type of knowledge, information, technology, or product is anticipated? - How will results be shared, who will have access, closed or open distribution? - What is the novelty, has it been reported before, what venues, the level of detail? - Are products of research transferable to other pathogens, applications - Does the research highlight vulnerability to existing practices, knowledge, counter

measures?

b) The ease with which the knowledge, technologies, or products might be misused and the associated feasibility.

- Consider the technical expertise and physical resources required. - Could the research products be directly misused and how? - Does other requirements/information already exist that could make this research

vulnerable for misuse? - What time frame implications exist to make this an immediate, or near future

threat?

c) The magnitude, nature and scope of potential consequences of misuse. - Consider what will be impacted: public health, agriculture, environment, economy,

or terrorism. - Degree of negative impact: minor, moderate or major. - Are there counter measures available to mitigate potential, and readily available.

4. Assess the benefits of the DC.

Note: Source of funding should be considered: scientific merit determined by funding agency input could be consulted. Material transfer agreements, contracts, and start –up funding may or may not consider this in terms of DURC implications.

- What is the benefit to public health and safety? - What are the contributions of this project to agriculture, economy, security...? - How will this research be beneficial to science, health and safety of our communities? - What is the time frame associated with the gain of benefits? - Who will gain the benefit (large or small impact), who will accept the risk?

5. Assist the PI in drafting a mitigation strategy

- Determine if existing biosafety and biosecurity measures are adequate. - Evaluate applicability of existing countermeasures. - Modify the experimental design or methodology to remove, reduce or mitigate the risk.




- Evaluate the efficacy of medical countermeasures against SSBA. - Consider experimentation timelines to reduce viability in external environment. - Develop a communication plan, defining what may/may not be distributed beyond the

lab, published or posted on line. - Determine the monitoring and report requirements to ensure the integrity and diligence

of the application of the measures implemented. - Determine if regulatory approval is required or recommended. - If appropriate measures cannot be found the research is denied.

6. Review (at least annually,) active DURC risk mitigation strategies.

- Determine what experimental results would require a reassessment prior to the annual review.

- Assess if research still aims to/or does incorporate the “experiments of concern”. - Evaluate the effectiveness of the mitigation strategy based on experimental results. - If the definition and the experimental outcomes no longer apply, withdraw the DURC

mitigation strategies.




REFERENCES: Tools for the Identification, Assessment, Management and Responsible Communication of Dual Use Research of Concern, A Companion Guide to the United States Government Policies for Oversight of Life Governing’dual-use”research in Canada: A Policy Review. Bryn Williams-Jones, Catherine Olivier and Elise Smith, Sicence and Public Policy (2013) pp1-18 Sciences Dual Use Research of Concern, Prepare by National Institute of Health, September 2014 Public Health Emergency - Science, Safety, Security Emergency https://www.phe.gov/s3/dualuse/Pages/default.aspx U.S. Government Gain-of-Function Deliberative Process and Research Funding Pause on Selected Gain-of-Function Research Involving Influenza, MERS, and SARS Viruses


https://www.phe.gov/s3/dualuse/Pages/default.aspx



APPENDIX C SECURITY SENSITIVE BIOLOGICAL AGENTS AND TOXINS http://www.phac-aspc.gc.ca/lab-bio/regul/ssba-abcse-eng.php

Security Sensitive Biological Agents List – Viruses • Andes virus • Chapare virus • Chikungunya virus • Choclo virus • Congo-Crimean haemorrhagic fever virus • Dobrava-Belgrade virus • Eastern equine encephalitis virus • Ebola virus • Guanarito virus • Hantaan virus • Hendra virus (Equine morbillivirus) • Highly pathogenic avian influenza virus • Japanese encephalitis virus • Junin virus • Kyasanur Forest virus • Laguna Negra virus • Lassa fever virus • Louping ill virus • Lujo virus • Machupo virus • Marburg virus • Monkey pox virus • Murray Valley encephalitis virus • Nipah virus • Omsk haemorrhagic fever virus • Oropouche virus • Powassan virus • Reconstructed 1918 influenza virus • Rift Valley fever virus • Rocio virus • Sabia virus • Seoul virus • Severe acute respiratory syndrome-related coronavirus (SARS-CoV) • Sin nombre virus


http://www.phac-aspc.gc.ca/lab-bio/regul/ssba-abcse-eng.php

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/chikungunya-eng.php

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/crim-congo-eng.php

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/equine-eng.php

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/ebola-eng.php

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/influenza-grippe-a-eng.php

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/msds173e-eng.php

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/junin-eng.php

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/kyasanur-eng.php

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/lassa-eng.php

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/machupo-eng.php

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/marburg-eng.php

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/orthopoxvirus-eng.php

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/arbovirus-eng.php

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/nipah-eng.php

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/omsk-eng.php




• St Louis encephalitis virus • Tick-borne encephalitis virus (Russian Spring-Summer encephalitis virus) • Variola virus • Venezuelan equine encephalitis virus • Western equine encephalitis virus • Yellow fever virus

Security Sensitive Biological Agents List – Bacteria • Bacillus anthracis • Brucella abortus • Brucella melitensis • Brucella suis • Chlamydophila psittaci (formerly known as Chlamydia psittaci) • Francisella tularensis • Burkholderia mallei (Pseudomonas mallei) • Burkholderia pseudomallei (Pseudomonas pseudomallei) • Yersinia pestis • Coxiella burnetii • Rickettsia prowazekii

Security Sensitive Biological Agents List – Toxins (and trigger quantity) • Alpha toxin (5 mg) • Botulinum neurotoxin (0.5 mg) • Cholera toxin (20 mg) • Clostridium botulinum C2 and C3 toxins (5 mg) • Clostridium perfringens Epsilon toxin (5 mg) • Hemolysin (10 mg) • Shiga-like toxin (verotoxin) (1 mg) • Shigatoxin (1mg) • Staphylococcus enterotoxins, Type B (1 mg) • Staphylococcus enterotoxins, types other than Type B (10 mg) • Staphylococcus aureus Toxic shock syndrome toxin (5 mg)

Security Sensitive Biological Agents List – Fungi • Coccidioides immitis • Coccidioides posadasii

Laboratories that work with strains of bacteria that produce SSBA toxins are not captured by the SSBA designation as long as the SSBA toxin is not produced to levels above the trigger quantity i. If work with strains of bacteria that produce SSBA toxins results in the production of quantities of SSBA toxins that exceed the SSBA toxin trigger quantities, the work would be subject to the SSBA designation.


http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/st-louis-encephalit-eng.php

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/variol-eng.php

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/ven-encephalit-eng.php

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/equine-eng.php

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/yfv-vfj-eng.php





http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/chlamydophila-psittaci-eng.php





http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/coxiella-burnetii-eng.php

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/rickettsia-prowazekii-eng.php

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/clostridium-eng.php

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/clostridium-perfringens-eng.php

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/staphylococcus-aureus-eng.php

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/coccidioides-spp-eng.php

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/coccidioides-spp-eng.php

http://www.phac-aspc.gc.ca/lab-bio/regul/ssba-abcse-eng.php#footnote1



APPENDIX B DUAL USE RESEARCH OF CONCERN REPORTING FORM

PART ONE RESEARCH REPORTING

Section A Principle Investigator

Name: Biomaterial Use Certificate #: Department: Phone #: Position: Email : Laboratory Room #.

Section B Person preparing this Document (if not PI)

Name: Phone#: Email: Position:

Section C Research Project

Title: Source of Funding: RE#, Contract # Start Date: End Date:

Attach Protocol to be used: Specific agent in use ____________________ SSBA: http://www.phac-aspc.gc.ca/lab-bio/regul/ssba-abcse-eng.php Source of Material:

Company: Individual: Address: Quantity:

Personnel:

Name Position DURC training Security Clearance


http://www.phac-aspc.gc.ca/lab-bio/regul/ssba-abcse-eng.php



Section D “Experiments of Concern” PI’s are required to assess their research project to determine if they contain SSBA or have experimental protocols that involve specific experimental protocols which increase the risk associated with the outcome. If at least one above criteria are met, a full DURC assessment must be undertaken.

1. Enhances the harmful consequences of the agent or toxin Yes No If yes, please explain how.

2. Disrupts immunity or the effectiveness of an immunization against the agent or toxin without clinical or agricultural justification. Yes No If yes, please explain how.

3. Confers to the agent or toxin resistance to clinically or agriculturally useful prophylactic ot therapeutic interventions against the agent or toxin or facilitates tits ability to evade detection methodology. Yes No If yes, please explain how.

4. Alters properties of the agent or toxin in a manner that would enhance its stability, transmissibility or ability to be disseminated. Yes No If yes, please explain how.

5. Alters the host range or tropism of the agent or toxin. Yes No If yes, please explain how.

6. Enhances the Susceptibility of a host population to the agent or toxin. Yes No If yes, please explain how.

7. Generates or reconstitutes an eradicated or extinct agent or toxin. Yes No If yes, please explain how.




PART TWO DURC RISK ASSESSMENT

Research knowledge, information, technology and products (KITP) could pose a risk of being misapplied and hence a threat to human, agriculture, environment, material and national security. The risk assessment is designed to identify:

- in what ways this could occur, - the ease by which this could occur by a third party, and - the magnitude, nature and scope of potential misuse.

1. The ways in which knowledge, information, technologies or products form research could be used to harm: people, crops, animals, environment, economy or security.

- What type of knowledge, information, technology, or product is anticipated? - How will results be shared, who will have access, closed or open distribution? - What is the novelty, has it been reported before, what venues, the level of detail? - Are products of research transferable to other pathogens, applications - Does the research highlight vulnerability to existing practices, knowledge, counter

measures?

d) The ease with which the knowledge, technologies, or products might be misused and the associated feasibility.

- Consider the technical expertise and physical resources required. - Could the research products be directly misused, and how? - Does other requirements/information already exist that could make this research

vulnerable for misuse? - What time frame implications exist to make this an immediate, or near future

threat?

e) The magnitude, nature and scope of potential consequences of misuse. - Consider what will be impacted: public health, agriculture, environment, economy,

or terrorism. - Degree of negative impact: minor, moderate or major. - Are there counter measures available to mitigate potential, and readily available.

2. Assess the benefits of the DC.

Note: Source of funding should be considered: scientific merit determined by funding agency input could be consulted. Material transfer agreements, contracts, and start –up funding may or may not consider this in terms of DURC implications.




- What is the benefit to public health and safety? - What are the contributions of this project to agriculture, economy, security...? - How will this research be beneficial to science, health and safety of our communities? - What is the time frame associated with the gain of benefits? - Who will gain the benefit (large or small impact), who will accept the risk?

3. Assist the PI in drafting a mitigation strategy

- Determine if existing biosafety and biosecurity measures are adequate. - Evaluate applicability of existing countermeasures. - Modify the experimental design or methodology to remove, reduce or mitigate the risk. - Evaluate the efficacy of medical countermeasures against SSBA. - Consider experimentation timelines to reduce viability in external environment. - Develop a communication plan, what may/may not be distributed beyond the lab,

published or posted on line. - Determine the monitoring and report requirements to ensure the integrity and diligence

of the application of the measures implemented. - Determine if regulatory approval is required or recommended. - If appropriate measures cannot be found the research is denied.

4. Review (at least annually,) active DURC risk mitigation strategies.

- Determine what experimental results would require a reassessment prior to the annual review.

- Assess if research still aims to/or does incorporate the “experiments of concern”. - Evaluate the effectiveness of the mitigation strategy based on experimental results. - If the definition and the experimental outcomes no longer apply, withdraw the DURC

mitigation strategies.


Documents

Biosecurity and The Evolving Concern regarding dual-use · smuggle 22 vials genetic m aterial out of the country. Some vials contained Ebola virus genes, subsequently deemed non-infectious